ABSTRACT: NATURAL HISTORY STUDIES ON THE INHERITED NEUROPATHIES Charcot Marie Tooth disease (CMT) is the eponym for heritable peripheral neuropathy. CMT affects approximately 1 in 2500 people and is divisible into three large sub-groups; CMT1 (dominantly inherited demyelinating neuropathies), CMT2 (dominantly inherited axonal neuropathies), and CMT4 (recessively inherited neuropathies). Mutations in more than 80 genes cause CMT1, CMT2 and CMT4. The biological basis for demyelination and axonal degeneration in these disorders has enabled rational therapy development for certain subtypes of CMT. Clinical trials, however, have been limited by a combination of a lack of natural history data, a lack of outcome measures that are sensitive to change in a short period of time, and a lack of outcome measures for young children with CMT. We have enrolled over 6500 participants into the protocols of the Inherited Neuropathy Consortium (INC) during our first cycle in the RDCRN. Support from our patient advocacy groups (PAGs) has allowed us to expand from 6 to 17 sites within the INC. Additional support from NINDS allowed us to develop the CMT-International Database (CMT-ID), a group of national CMT registries who also use the CMT Minimal Dataset and house their data at the DMCC. We have a unique opportunity to obtain and evaluate patients with rare forms of inherited neuropathy. We propose to extend our work during the upcoming cycle with the following Specific Aims: Aim 1: Expand natural history investigations on CMT1A, CMT1B, CMT1X and CMT2A: Aim 2: Accrue and evaluate patients with rare forms of CMT. Aim 3: Validate and test patient reported disability and quality of life (QOL) instruments in adults with CMT Aim 4: Validate infant-toddler disability and QOL instruments in children with CMT.